Postmarketing Clinical Study on AO-128

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02287402
• Collaborator: (none)
• Enrollment: 197
• Arm: 1
• Duration (Months): 32.1

Study Details

Study Description

Brief Summary

The purpose of open-label study is to evaluate the efficacy and safety of AO-128 (Voglibose) 0.6 mg/day in patients with impaired glucose tolerance (IGT) who had been non-responsive to diet therapy and exercise therapy, and follow up the progress after the end of treatment in patients who was assessed as normoglycemic.

Condition or Disease	Intervention/Treatment	Phase
Impaired Glucose Tolerance (IGT)	Drug: AO-128	Phase 4

Detailed Description

The α-glucosidase inhibitor voglibose was developed by Takeda Pharmaceutical Co. Ltd and is one of the most commonly used oral antidiabetic agents in Japan. Voglibose is used as first-line treatment for improvement of postprandial hyperglycemia in diabetic patients with inadequate response to diet and exercise therapy and as add-on treatment to other oral antidiabetic drugs and insulin. In 2009, voglibose was approved in Japan for the management of prediabetes (IGT).

This study was a single-group, multi-center, open-label study. The study period consisted of a screening period of 1 week or less, a treatment period of 96 weeks or more, and a follow-up period of 48 weeks. However, if a patient was assessed as having type 2 diabetes mellitus or normoglycemia, the treatment period was to be ended, and only those assessed as normoglycemic were to proceed to follow-up. Follow-up was also to be terminated if patients were assessed as having IGT or type 2 diabetes mellitus during follow-up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 197 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Postmarketing Clinical Study on AO-128
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AO-128 0.6 mg One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.	Drug: AO-128; AO-128 tablet; Other Names: Voglibose BASEN

Outcome Measures

Primary Outcome Measures

1. Assessment of Diabetic Status in the Treatment Period (Type 2 Diabetes Mellitus, Normoglycemia, or Impaired Glucose Tolerance (IGT) [Treatment period: Up to 122 weeks. Treatment was to be ended when patients were assessed as Type 2 Diabetes Mellitus or normoglycemic.]

   Frequency tabulations of the "assessment of diabetic status in the treatment period (Type 2 Diabetes mellitus, normoglycemia, or IGT)" were prepared in the "Full Analysis Set".

2. Assessment of Diabetic Status in Follow-up (Type 2 Diabetes Mellitus, Normoglycemia, or IGT) [Follow-up at Week 12, 24, 36, and 48]

   Frequency tabulations of the "assessment of diabetic status in the follow-up (Type 2 Diabetes mellitus, normoglycemia, or IGT)" were prepared in patients who proceeded to the follow-up in the "Full Analysis Set".

Secondary Outcome Measures

1. Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated by the Kaplan-Meier Method [Day 168, 336, 504, and 672]

   The cumulative progression rate (percentage of participants) was calculated by the Kaplan-Meier method for the "time to progression to Type 2 Diabetes mellitus in the treatment period" in the "Full Analysis Set".

2. Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated Using the Cumulative Incidence Function [Day 168, 336, 504, and 672]

   The cumulative progression rate (percentage of participants) was calculated using the cumulative incidence function for the "time to progression to type 2 diabetes mellitus in the treatment period" in the "Full Analysis Set".

3. Time to Improvement to Normoglycemia in the Treatment Period Calculated by the Kaplan-Meier Method [Day 168, 336, 504, and 672]

   The cumulative progression rate (percentage of participants) was calculated by the Kaplan-Meier method for the "time to improvement to normoglycemia in the treatment period" in the "Full Analysis Set".

4. Time to Improvement to Normoglycemia in the Treatment Period Measured Values by the Cumulative Incidence Function [Day 168, 336, 504, and 672]

   The cumulative progression rate (percentage of participants) was calculated using the cumulative incidence function for the "time to improvement to normoglycemia in the treatment period" in the "Full Analysis Set".

5. 2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT) [Week 0, 24, 48, 72, 96, 120, and the end of the treatment period]

   Summary statistics were calculated at each assessment time point for the 2-hour plasma glucose during 75 g OGTT in the "Full Analysis Set."

6. 2-Hour Plasma Glucose During 75 g OGTT at Follow-up [Follow-up at week 0, 12, 24, 36, and 48]

   Summary statistics were calculated at each assessment time point for the 2-hour plasma glucose during 75 g OGTT in participants who proceeded to the follow-up in the "Full Analysis Set."

7. Hemoglobin A1c (HbA1c) [Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period.]

   Summary statistics were calculated at each assessment time point for the HbA1c in the "Full Analysis Set."

8. HbA1c at Follow-up [Follow-up at Week 0, 12, 24, 36, and 48]

   Summary statistics were calculated at each assessment time point for the HbA1c in patients who proceeded to the follow-up in the "Full Analysis Set."

9. Body Weight [Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period]

   Summary statistics were calculated at each assessment time point for the body weight in the "Full Analysis Set."

10. Body Weight at Follow-up [Follow-up at Week 0, 12, 24, 36, and 48]

    Summary statistics were calculated at each assessment time point for the HbA1c in patients who proceeded to the follow-up in the "Full Analysis Set."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients on diet therapy and exercise therapy for 3 to 6 months prior to the start of screening, with baseline (fasting ) plasma glucose < 126 mg/dL and 2-hour plasma glucose of 140 to 199 mg/dL (revised WHO criteria) during a 75 g oral glucose tolerance test (OGTT) in the screening period

2. Patients meeting any of 1 through 4 below:

• 1. Comorbid hypertension or high normal blood pressure
• 1. Comorbid dyslipidemia
• 1. Comorbid obesity
• 1. Patients with up to a second-degree family history of type 2 diabetes mellitus

1. Patients with HbA1c < 6.5% in the screening period

2. Male or female patients at least 20 years of age at the time informed consent was obtained

3. Treatment category: Outpatient

Exclusion Criteria:

1. Patients previously diagnosed with diabetes mellitus.

2. Patients with apparent impaired glucose metabolism or with a disease or condition potentially involving impaired glucose metabolism.

3. Patients with serious hepatic impairment.

4. Patients with serious renal impairment.

5. Patients with serious cardiac, cerebrovascular, pancreatic, hematologic, or other disease.

6. Patients with a history of intestinal obstruction or a history of laparotomy within 6 months (24 weeks) before the start of screening.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02287402
• Other Study ID Numbers: AO-128/OCT-910; JapicCTI-101004; U1111-1163-1618
• First Posted: Nov 10, 2014
• Last Update Posted: Apr 9, 2015
• Last Verified: Apr 1, 2015

• Additional relevant MeSH terms: Glucose Intolerance; Voglibose

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 30 investigative sites in Japan from 9 March 2010 to 15 November 2012.
Pre-assignment Detail	Participants with impaired glucose tolerance (IGT) who had been non-responsive to diet therapy and exercise therapy receive one AO-128 0.2 mg tablet orally 3 times a day before meals.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Period Title: Treatment Period
STARTED	197
COMPLETED	170
NOT COMPLETED	27
Period Title: Treatment Period
STARTED	106
COMPLETED	103
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Overall Participants	197
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (9.35)
Age, Customized (participants) [Number]
<65 years	137 69.5%
≥65 years	60 30.5%
Sex: Female, Male (Count of Participants)
Female	68 34.5%
Male	129 65.5%
Region of Enrollment (participants) [Number]
Japan	197 100%

Outcome Measures

1. Primary Outcome

Title	Assessment of Diabetic Status in the Treatment Period (Type 2 Diabetes Mellitus, Normoglycemia, or Impaired Glucose Tolerance (IGT)
Description	Frequency tabulations of the "assessment of diabetic status in the treatment period (Type 2 Diabetes mellitus, normoglycemia, or IGT)" were prepared in the "Full Analysis Set".
Time Frame	Treatment period: Up to 122 weeks. Treatment was to be ended when patients were assessed as Type 2 Diabetes Mellitus or normoglycemic.

Outcome Measure Data

Analysis Population Description

Full Analysis Set - All participants who received at least 1 dose of open-label study drug.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	197
Type 2 Diabetes mellitus	25 12.7%
Normoglycemia	106 53.8%
IGT	66 33.5%

2. Primary Outcome

Title	Assessment of Diabetic Status in Follow-up (Type 2 Diabetes Mellitus, Normoglycemia, or IGT)
Description	Frequency tabulations of the "assessment of diabetic status in the follow-up (Type 2 Diabetes mellitus, normoglycemia, or IGT)" were prepared in patients who proceeded to the follow-up in the "Full Analysis Set".
Time Frame	Follow-up at Week 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set, all participants who received at least 1 dose of open-label study drug, and continued to Follow-up.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	106
Type 2 Diabetes mellitus	3 1.5%
Normoglycemia	9 4.6%
IGT	94 47.7%

3. Secondary Outcome

Title	Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated by the Kaplan-Meier Method
Description	The cumulative progression rate (percentage of participants) was calculated by the Kaplan-Meier method for the "time to progression to Type 2 Diabetes mellitus in the treatment period" in the "Full Analysis Set".
Time Frame	Day 168, 336, 504, and 672

Outcome Measure Data

Analysis Population Description

Full Analysis Set - All participants who received at least 1 dose of open-label study drug.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	197
Day 168	0.0 0%
Day 336	4.4 2.2%
Day 504	10.2 5.2%
Day 672	16.9 8.6%

4. Secondary Outcome

Title	Time to Progression to Type 2 Diabetes Mellitus in the Treatment Period Calculated Using the Cumulative Incidence Function
Description	The cumulative progression rate (percentage of participants) was calculated using the cumulative incidence function for the "time to progression to type 2 diabetes mellitus in the treatment period" in the "Full Analysis Set".
Time Frame	Day 168, 336, 504, and 672

Outcome Measure Data

Analysis Population Description

Full Analysis Set - All participants who received at least 1 dose of open-label study drug.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	197
Day 168	0.0 0%
Day 336	3.3 1.7%
Day 504	6.9 3.5%
Day 672	10.0 5.1%

5. Secondary Outcome

Title	Time to Improvement to Normoglycemia in the Treatment Period Calculated by the Kaplan-Meier Method
Description	The cumulative progression rate (percentage of participants) was calculated by the Kaplan-Meier method for the "time to improvement to normoglycemia in the treatment period" in the "Full Analysis Set".
Time Frame	Day 168, 336, 504, and 672

Outcome Measure Data

Analysis Population Description

Full Analysis Set - All participants who received at least 1 dose of open-label study drug.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	197
Day 168	18.9 9.6%
Day 336	37.5 19%
Day 504	50.2 25.5%
Day 672	60.3 30.6%

6. Secondary Outcome

Title	Time to Improvement to Normoglycemia in the Treatment Period Measured Values by the Cumulative Incidence Function
Description	The cumulative progression rate (percentage of participants) was calculated using the cumulative incidence function for the "time to improvement to normoglycemia in the treatment period" in the "Full Analysis Set".
Time Frame	Day 168, 336, 504, and 672

Outcome Measure Data

Analysis Population Description

Full Analysis Set - All participants who received at least 1 dose of open-label study drug.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	197
Day 168	18.9 9.6%
Day 336	36.9 18.7%
Day 504	48.4 24.6%
Day 672	57.1 29%

7. Secondary Outcome

Title	2-Hour Plasma Glucose During 75 g Oral Glucose Tolerance Test (OGTT)
Description	Summary statistics were calculated at each assessment time point for the 2-hour plasma glucose during 75 g OGTT in the "Full Analysis Set."
Time Frame	Week 0, 24, 48, 72, 96, 120, and the end of the treatment period

Outcome Measure Data

Analysis Population Description

Full Analysis Set - All participants who received at least 1 dose of open-label study drug.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	197
Week 0	166.7 (17.34)
Week 24	148.0 (34.30)
Week 48	153.2 (36.58)
Week 72	155.6 (36.77)
Week 96	155.6 (33.17)
Week 120	163.2 (31.89)
The end of the treatment period	142.8 (37.73)

8. Secondary Outcome

Title	2-Hour Plasma Glucose During 75 g OGTT at Follow-up
Description	Summary statistics were calculated at each assessment time point for the 2-hour plasma glucose during 75 g OGTT in participants who proceeded to the follow-up in the "Full Analysis Set."
Time Frame	Follow-up at week 0, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set, all participants who received at least 1 dose of open-label study drug, and continued to Follow-up.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	106
Follow-up at Week 0	119.4 (15.82)
Follow-up at Week 12	148.3 (35.26)
Follow-up at Week 24	147.9 (29.69)
Follow-up at Week 36	145.9 (18.94)
Follow-up at Week 48	138.3 (20.06)

9. Secondary Outcome

Title	Hemoglobin A1c (HbA1c)
Description	Summary statistics were calculated at each assessment time point for the HbA1c in the "Full Analysis Set."
Time Frame	Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period.

Outcome Measure Data

Analysis Population Description

Full Analysis Set - All participants who received at least 1 dose of open-label study drug.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	197
Week 0	5.45 (0.331)
Week 12	5.35 (0.305)
Week 24	5.30 (0.302)
Week 48	5.37 (0.317)
Week 72	5.34 (0.285)
Week 96	5.41 (0.269)
Week 120	5.45 (0.256)
The end of the treatment period	5.35 (0.323)

10. Secondary Outcome

Title	HbA1c at Follow-up
Description	Summary statistics were calculated at each assessment time point for the HbA1c in patients who proceeded to the follow-up in the "Full Analysis Set."
Time Frame	Follow-up at Week 0, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set, all participants who received at least 1 dose of open-label study drug, and continued to Follow-up.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	106
Follow-up at Week 0	5.23 (0.292)
Follow-up at Week 12	5.27 (0.330)
Follow-up at Week 24	5.26 (0.326)
Follow-up at Week 36	5.20 (0.301)
Follow-up at Week 48	5.28 (0.260)

11. Secondary Outcome

Title	Body Weight
Description	Summary statistics were calculated at each assessment time point for the body weight in the "Full Analysis Set."
Time Frame	Week 0, 12, 24, 48, 72, 96, 120, and the end of the treatment period

Outcome Measure Data

Analysis Population Description

Full Analysis Set - All participants who received at least 1 dose of open-label study drug.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	197
Week 0	70.74 (13.708)
Week 12	69.74 (13.659)
Week 24	69.91 (13.658)
Week 48	69.25 (13.632)
Week 72	70.03 (13.955)
Week 96	69.25 (14.484)
Week 120	68.82 (14.835)
The end of the treatment period	68.96 (13.892)

12. Secondary Outcome

Title	Body Weight at Follow-up
Description	Summary statistics were calculated at each assessment time point for the HbA1c in patients who proceeded to the follow-up in the "Full Analysis Set."
Time Frame	Follow-up at Week 0, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set, all participants who received at least 1 dose of open-label study drug, and continued to Follow-up.

Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
Measure Participants	106
Follow-up at Week 0	67.60 (13.023)
Follow-up at Week 12	67.76 (13.035)
Follow-up at Week 24	68.87 (11.703)
Follow-up at Week 36	70.13 (11.754)
Follow-up at Week 48	68.72 (13.844)

Adverse Events

Time Frame	From the first dose of open-label study drug until the day of the last dose of open-label study drug.
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	AO-128 0.6 mg
Arm/Group Description	One AO-128 0.2 mg tablet was taken orally 3 times a day before meals.
All Cause Mortality
	AO-128 0.6 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	AO-128 0.6 mg
	Affected / at Risk (%)	# Events
Total	15/197 (7.6%)
Cardiac disorders
Cardiac failure	1/197 (0.5%)
Eye disorders
Cataract	2/197 (1%)
Infections and infestations
Pneumonia	1/197 (0.5%)
Sinusitis	1/197 (0.5%)
Herpes zoster oticus	1/197 (0.5%)
Gastroenteritis norovirus	1/197 (0.5%)
Injury, poisoning and procedural complications
Meniscus lesion	1/197 (0.5%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/197 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer stage 0	1/197 (0.5%)
Nervous system disorders
Nystagmus	1/197 (0.5%)
Renal and urinary disorders
Calculus urinary	2/197 (1%)
Calculus ureteric	1/197 (0.5%)
Nephrolithiasis	1/197 (0.5%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/197 (0.5%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/197 (1%)
Nasal septum deviation	1/197 (0.5%)
Other (Not Including Serious) Adverse Events
	AO-128 0.6 mg
	Affected / at Risk (%)	# Events
Total	165/197 (83.8%)
Gastrointestinal disorders
Diarrhoea	29/197 (14.7%)
Flatulence	28/197 (14.2%)
Abdominal distension	26/197 (13.2%)
Constipation	10/197 (5.1%)
Immune system disorders
Seasonal allergy	7/197 (3.6%)
Infections and infestations
Nasopharyngitis	52/197 (26.4%)
Influenza	8/197 (4.1%)
Pharyngitis	7/197 (3.6%)
Bronchitis	6/197 (3%)
Gastroenteritis	6/197 (3%)
Injury, poisoning and procedural complications
Contusion	7/197 (3.6%)
Investigations
Alanine aminotransferase increased	6/197 (3%)
Musculoskeletal and connective tissue disorders
Myalgia	6/197 (3%)
Nervous system disorders
Headache	7/197 (3.6%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	14/197 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The clinical trial contract states that information should never be disclosed without prior consent of the sponsor, although it does not specify the number of days during which disclosure of information is limited.